The long term objective of this proposal is to elucidate the interrelationships between the immune effector cells of Balb/c mice and their interactions with syngeneic mammary tumors of viral and non-viral origin developing in these hosts. The model systems to be employed include the Balb/cCrgl mouse colony where only endogenous mouse mammary tumor virus (MMTV) is present, Balb/cfC3H mice where in addition to the endogenous virus the exogenous MMTV has been introduced by foster nursing, and a colony of immunodeficient Balb/c mice which includes mice with inherited asplenia and heterozygous for the nude gene that have been shown to possess a very high incidence of spontaneous mammary tumors at an early age. The expression of MMTV-related antigens in lymphocytes will be analyzed at the transcriptional and translational levels in the Balb/cCrgl, Balb/cfC3H and in the immunodeficient Balb/c mice of the various genotypes. The relevance of endogenous MMTV as well as the modulating effects of exogenous virus to the host immune defenses will be assessed. Various regulatory cells detected in our previous studies that affect the responses to MMTV and to tumor associated antigens (TAA), will be analyzed by morphological, surface marker characteristics and functional activities. The mechanisms of action governing several cytotoxic reactions, i.e. NK, ADCC and innocent bystander cytotoxicity, will be scrutinized in the context of their effector cells, modulating factors and alterations during tumor growth. The possible reasons for the lack of responsiveness to TAA of the tumor infiltrating lymphocytes will be investigated. The proposed studies, which are logical derivations of our ongoing program, will help our understanding of the relative contributions of the various viral and tumor antigenic moieties and of the different types of lymphoreticular cells to the final outcome of the host-tumor interactions.